SUMMARY While total knee replacement (TKR) is regarded as a reasonably successful procedure in terms of revision rates (95% survivorship at 10 years), about 25% of patients remain dissatisfied with the outcome of their surgery. Moreover, nearly half of early TKR revisions are considered preventable if surgical techniques could reliably provide for proper component alignment and ligament balance. Considering that the number of TKR in the USA is projected to exceed 4.3 million annually by 2030, this equates to millions of dissatisfied patients with unsatisfactory clinical outcomes. It is well-established that stable TKR function is critical for successful patient outcomes. During TKR surgery, surgeons perform manual evaluations to detect joint instability and proceed to correct it by adjusting the TKR alignment and balancing the tension in the soft tissues surrounding the joint. Unfortunately, there is little evidence to guide surgeons in determining when alignment and soft tissue tension are adequate. It has long been speculated that soft tissue tension profiles could be a predictor of TKR clinical outcome compared to component alignment. Based on our published clinical studies, it is our scientific premise that alignment impacts soft tissue tension and the stability perceived by the patients, contributing to poor clinical scores. However, adequate methods for measuring soft tissue tension in vivo do not exist and the internal mechanical environment in the knee after TKR is poorly defined. Our long-term goal is to develop a validated finite element (FE) model of TKR and use it to determine the tension profiles of nine individual soft tissue structures crossing the knee joint and to establish quantitative relationships between component alignment, soft tissue tension, and clinical outcome in TKR patients. We hypothesize that i) component alignment affects soft tissue tension conditions during TKR; and ii) these soft tissue conditions are significant predictors of clinical outcomes after TKR. We propose to address these knowledge and technical gaps using a unique experimental and computational modeling approach. We identify the following specific aims: 1) adapt a finite element model of the natural knee to evaluate soft tissue tension in TKR; 2) determine the effect of TKR alignment on soft tissue tension; and 3) determine the effect of tension profiles on in vivo clinical outcomes of TKR. Successful completion of this proposal will: i) demonstrate the practical use of intra-operative measurements of knee kinematics during passive range of motion (ROM) for determining soft-tension profiles in FE TKR models and; ii) identify potential predictors of poor functional outcomes related to component alignment and soft tissue tension; and iii) identify potential detectable events that could inform technology innovation for more meaningful use of intra-operative sensing of soft tissue tension and knee motions. This project will inform our future R01 proposals addressing the magnitude of clinically acceptable soft tissue tension and the influence of different TKR designs and surgical techniques on soft tissue tension.